1-167114466-A-G

Variant names:

• chr1-167114466-A-G
• rs950303
• NM_001080426.3:c.205+662A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001080426.3(STYXL2):​c.205+662A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.655 in 152,078 control chromosomes in the GnomAD database, including 33,957 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (33957 hom., cov: 31)
• Consequence: STYXL2 NM_001080426.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696
• Publications: 1 publications found

Genes affected

STYXL2 (HGNC:25034): (serine/threonine/tyrosine interacting like 2) Predicted to enable protein tyrosine/serine/threonine phosphatase activity. Predicted to be involved in protein dephosphorylation. Predicted to be located in sarcomere. [provided by Alliance of Genome Resources, Apr 2022]

GPA33 (HGNC:4445): (glycoprotein A33) The glycoprotein encoded by this gene is a cell surface antigen that is expressed in greater than 95% of human colon cancers. The open reading frame encodes a 319-amino acid polypeptide having a putative secretory signal sequence and 3 potential glycosylation sites. The predicted mature protein has a 213-amino acid extracellular region, a single transmembrane domain, and a 62-amino acid intracellular tail. The sequence of the extracellular region contains 2 domains characteristic of the CD2 subgroup of the immunoglobulin (Ig) superfamily. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STYXL2	NM_001080426.3	c.205+662A>G		intron_variant	Intron 3 of 5	ENST00000361200.7	NP_001073895.1
STYXL2	XM_011510146.3	c.88+662A>G		intron_variant	Intron 2 of 4		XP_011508448.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
STYXL2	ENST00000361200.7	c.205+662A>G		intron_variant	Intron 3 of 5	5	NM_001080426.3	ENSP00000354483.2
STYXL2	ENST00000271385.9	c.205+662A>G		intron_variant	Intron 3 of 5	1		ENSP00000271385.5
STYXL2	ENST00000443333.1	c.205+662A>G		intron_variant	Intron 2 of 4	5		ENSP00000404874.1
GPA33	ENST00000632571.1	c.-281-40927T>C		intron_variant	Intron 1 of 3	4		ENSP00000488407.1

Frequencies

GnomAD3 genomes AF: 0.655 AC: 99495 AN: 151960 Hom.: 33914 Cov.: 31

Gnomad AFR AF: 0.835

Gnomad AMI AF: 0.576

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.607

Gnomad EAS AF: 0.899

Gnomad SAS AF: 0.478

Gnomad FIN AF: 0.578

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.581

Gnomad OTH AF: 0.648

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.655 AC: 99588 AN: 152078 Hom.: 33957 Cov.: 31 AF XY: 0.650 AC XY: 48344 AN XY: 74356

African (AFR) AF: 0.835 AC: 34665 AN: 41494

American (AMR) AF: 0.539 AC: 8232 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.607 AC: 2103 AN: 3466

East Asian (EAS) AF: 0.900 AC: 4657 AN: 5176

South Asian (SAS) AF: 0.478 AC: 2296 AN: 4804

European-Finnish (FIN) AF: 0.578 AC: 6121 AN: 10592

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.580 AC: 39441 AN: 67946

Other (OTH) AF: 0.651 AC: 1373 AN: 2108

Alfa AF: 0.606 Hom.: 6068

Bravo AF: 0.666

Asia WGS AF: 0.702 AC: 2444 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.44
PhyloP100		-0.70
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs950303; hg19: chr1-167083703;